Effect of prolonged glucose infusion on insulin sensitivity in the conscious normal rat.

Abstract

It has been proposed that hyperglycemia contributes to the insulin resistance normally seen in non-insulin-dependent diabetes mellitus (DeFronzo, Simonson and Ferrannini 1982; Kolterman, Gray, Griffen, Burstein, Insel, Scarlett and Olefsky 1981 ). Fasting hyperglycemia is correlated to the severity of insulin resistance in human type II diabetes (Kolterman, Gray, Griffen, Burstein, Insel, Scarlett and Olefsky 1981) and reductions of hyperglycemia produced by insulin therapy have been shown to reduce the degree of insulin resistance (Garvey, Olefsky, Griffen, Hamman and Kolterman 1985). Insulin resistance has been reversed in insulinopenic states such as in insulin-dependent diabetic subjects (Foss, Vlachoksta, Cunningham and Aoki 1982) or in experimental diabetes induced in the rat (Rossetti, Smith, Shulman, Papachristou and DeFronzo 1987). The hyperglycemia, hyperinsulinemia and glucosuria developed in intact rats receiving a 50 % glucose intravenous infusion (60-66 mg/kg/min) for 72 h have been shown to produce insulin resistance (Hager,Jochen and Kalkhoff 1991 ). However, conditions of prolonged hyperinsulinemia in the presence of different degrees of hypoglycemia have been shown to either decrease (Whittaker, Alberti, York and Singh 1979) or increase (Trimble, Weir, Gjinovci, Assimacopoulos-Jeannet, Benzi and Renold 1984; Wardzala, Hirshman, Pofcher, Horton, Mead, Cushman and Horton 1985) insulin sensitivity. The present study was addressed both to testing a method for developing continuous hyperinsulinemia in the conscious normal rat and to studying further the role of hyperinsulinemia in the potential changes of insulin sensitivity in this species.